RSTMH Early Career Grant Programme case study 1: Project statement

Many early career researchers ask us what makes a good Early Career Grant application, and how they should tackle certain parts of the application form, particularly as they are applying for a grant for the first time.

To try and help with this we will be starting to include examples of good elements of the application form, for you to look at.

In the first instance we are including a few examples of a high quality project statement, which is the part of the form where you lay out your background, aims, methods and expected outcomes for the project. This first example below is of a high standard for the following reasons 

  • It is well structured, the applicant has used the suggested headings to break up this long statement into the important aspects of the project 
  • Using the main headings also makes it easier for assessors to understand the project better and to consider its quality
  • They have explained any acronyms used e.g. STH and NTDs. If you need to use them to save space make sure you write them in full the first time they are used 
  • They have quantified the problem well, which sets the scene for the importance of this piece of research 
  • The language used throughout the statement is easy to follow and to understand, it avoids overly complicated and lengthy terms 
  • Overall the project statement is succinct, it is not repetitive, and sticks clearly to the headings suggested  

We are also running some detailed guidance sessions for our members on the 24th March, where we will look in more detail at how you convert an idea into a research question, how you select the right methodology, how to construct a budget and how to consider the outcomes. This session will be recorded and will be posted in the members area for you to look at.
 

1) Project background, context and need addressed

Soil-transmitted helminths (STH) remain one of the most prevalent parasitic diseases of humans worldwide, with an estimated 894 million people infected [1]. Like other neglected tropical diseases (NTDs), STH predominantly affect those living in poverty, and perpetuate the cycle of poverty in afflicted populations. STH are transmitted when individuals accidentally ingest — or have their skin penetrated by — infective parasite stages, following soil contamination by infected individuals’ faeces. Infections are treatable using deworming medications, typically albendazole or mebendazole. However, reinfection often occurs rapidly following deworming in the context of ongoing environmental contamination [2]. Chronic, heavy-intensity infections lead to impaired child growth and development and iron-deficiency anaemia, with children and women of childbearing age at highest risk of STH-associated morbidity [3].

Encouragingly, there has been significant progress towards controlling STH infections globally since the landmark London Declaration on NTDs in 2012. As part of a concerted global effort to improve NTD control, deworming programs for STH control have been scaled up worldwide, with over 746 million children treated in large-scale deworming campaigns in 2017 [4].

Diagnostic methods for detecting and quantifying STH represent a crucial component of STH control efforts. Knowledge of infection prevalence and intensity in target populations and communities is critical for planning STH control programs, and monitoring and evaluating their impact. As deworming programs are scaled up worldwide, accurate determination of disease levels in populations after long-term deworming efforts becomes increasingly important, in order to inform decisions regarding ongoing control efforts. However, the existing, microscopy-based diagnostic techniques that are generally used to detect and quantify STH infections are known to have low sensitivity in low-transmission settings [5]. Therefore, more sensitive diagnostic techniques are required.

Molecular diagnostic techniques such as quantitative PCR (qPCR) have recently been investigated as tools for detecting and quantifying STH infections. qPCR uses DNA primers and probes to amplify and detect specific DNA sequences. This technique has consistently demonstrated higher diagnostic sensitivity compared to traditional microscopy-based methods [6, 7]. qPCR assays also provide a quantitative measure of infection by measuring the number of DNA amplification cycles required to detect a signal exceeding background levels. qPCR’s high sensitivity, along with its ability to measure infection intensity, has generated significant interest among STH researchers in its applicability for monitoring the impact of large-scale STH control programs. Although more expensive than microscopy-based methods, modelling studies show that more sensitive diagnostic techniques may be more cost-effective long term [8].

However, to date the use of qPCR has been limited mainly to relatively small-scale research projects, and has not yet been examined in the context of large-scale deworming. In order to inform NTD policymakers, it is crucial to conduct research on qPCR within large-scale deworming programs. In particular, research is required to compare diagnostic sensitivity and infection intensity measurements obtained using qPCR and conventional microscopy-based techniques, before and after implementation of large-scale deworming. This will facilitate an understanding of the performance of qPCR in measuring the impact of STH control programs. Additionally, ongoing work is required in order to convert infection intensity measurements obtained using qPCR into the current standard measurement of eggs per gram (EPG) of faeces, such that qPCR results can be interpreted in a clinically relevant context, and existing cut-offs for light, moderate, and heavy intensity infections applied.

Here, funding is sought to conduct a comparison of qPCR and sodium nitrate flotation, a microscopy-based technique, within the context of a large deworming trial in Vietnam. This project will provide key information for NTD policymakers regarding the performance of qPCR in the context of large-scale deworming programs. This research will contribute to the evidence base surrounding the applicability of molecular diagnostic techniques to STH control programs.


2) Aims/research questions being addressed

The aims of this project are to:
a) Compare the diagnostic sensitivity of qPCR and sodium nitrate flotation for STH infections, both before and six months following large-scale deworming; and
b) Examine the relationship between STH infection intensity measurements obtained using qPCR (Ct values) and sodium nitrate flotation (eggs per gram of faeces), both before and six months following large-scale deworming.


3) Study design

This project will be implemented as a nested study with an existing trial, the CoDe-STH (Community Deworming against Soil-Transmitted Helminths) trial. The CoDe-STH trial is funded by the National Health & Medical Research Council, Australia (APP1139561).

CoDe-STH is a cluster-randomised controlled trial that will be conducted in 64 primary schools in Dak Lak province, Vietnam. The primary aim of the trial is to compare the impact of school-based (targeted) deworming and community-wide (mass) deworming on STH infection prevalence in school-aged children. The trial intervention consists of two rounds of deworming, six months apart. In each of these two rounds, approximately 38,000 doses of albendazole will be delivered to school-aged children across the two study arms, and a further 57,000 doses to other community members in the intervention arm only. Approximately 7500 children will be recruited for data collection, which will involve providing a stool sample at three time points:
- study baseline (immediately before the first deworming round);
- six months following the first deworming round (immediately before the second deworming round); and
- six months following the second deworming round.

Within the CoDe-STH trial, STH infections will be measured in study participants at each study time point using quantitative PCR, performed at the University of Melbourne.

To allow for a comparison between qPCR and microscopy-based diagnosis, the project described in this funding application will additionally measure STH infections using sodium nitrate flotation in a subset of study participants. STH infections will be diagnosed using sodium nitrate flotation in 5000 study participants, approximately 80 children per study school. This will be done at both study baseline and at the first six-month follow-up, such that qPCR can be compared to sodium nitrate flotation both before and after large-scale deworming. Sodium nitrate flotation will be performed at Tay Nguyen University in Vietnam.


4) Approach used to maximise the impact of research outputs, to improve health and the research community

This project aims to further the understanding of the performance of qPCR for STH diagnosis within the context of large-scale deworming. This is being done primarily to inform policymakers and contribute to the evidence base regarding the use of molecular diagnostic techniques to monitor the impact of deworming programs. Ultimately this research could contribute to the inclusion of molecular diagnostic techniques in guidelines for STH control program implementers, allowing for improved monitoring of program impact. The results of this project will be written up as at least one journal article, with a focus on the interpretation of study findings in terms of STH control guidelines and policies. Study results will also be presented to the research community and other stakeholders during at least one international conference. Furthermore, study results will be presented to local stakeholders in Vietnam, including the Ministry of Health and the Centre for Parasitic Disease Control & Prevention.


5) Expected outcomes

The primary outcomes of this study will be the prevalence of each STH species using qPCR and sodium nitrate flotation, and the mean infection intensity of each STH species using qPCR and sodium nitrate flotation. These outcomes will be measured at baseline and six months’ follow-up. Statistical analysis will be conducted to compare the two diagnostic techniques at each time point. The sensitivity of each diagnostic technique for each STH species will be calculated by considering an individual to be “true positive” if they have a positive result by either technique, qPCR or sodium nitrate flotation. Diagnostic agreement will be tested using Kappa statistics. Spearman’s rank correlation coefficients will be used to examine the association between PCR-determined infection intensity and EPG values.

It is expected that this project will yield valuable evidence regarding the performance of qPCR within the context of large-scale deworming campaigns that could contribute to changing policy. The results of this project will be written up as at least one journal article, with emphasis given to the interpretation of study findings in terms of STH control guidelines and policies. Results will also be presented to the research community and other stakeholders during at least one international conference.


6) My role in the project

My role in this side project will be that of project coordinator – I will oversee data collection and data entry. I will lead the statistical analysis, interpretation, and the preparation of at least one journal article.

References

1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. https://doi.org/10.1016/S0140-6736(18)32279-7
2. Jia TW et al. https://doi.org/10.1371/journal.pntd.0001621
3. Bethony J et al. https://doi.org/10.1016/S0140-6736(06)68653-4
4. WHO. https://www.who.int/neglected_diseases/resources/who_wer9350/en/
5. Nikolay B et al. https://doi.org/10.1016/j.ijpara.2014.05.009
6. Easton AV et al. https://doi.org/10.1186/s13071-016-1314-y
7. Clarke NE et al. https://doi.org/10.4269/ajtmh.18-0356
8. Turner HC et al. https://doi.org/10.1016/j.pt.2017.01.007